This laboratory has been working towards characterizing the possible receptor mechanisms responsible for the therapeutic and side effects of the estrogenic component of the oral contraceptives. We have found a high affinity estradiol specific binding protein in the cytosol of the adult female mammalian liver. This may be the estrogen receptor based upon its capability to translocate to the nucleus and to attach to chromatin. We postulate that this estrogen receptor in liver may be involved in production of the side effects by increasing synthesis of selective plasma proteins including clotting factors (involved in thromboembolism), renin substrate (involved in hypertension) or lipoproteins (potentially involved in accelerating atherosclerosis). The present request proposes studying: (1) the human liver in vitro for the estrogen receptor and the influence of metabolism on this binding; (2) additional properties of the cytoplasmic and nuclear binding of estrogens in the rat liver including further purification and correlation of the development of the liver binding protein with sexual maturation to changes in the liver produced by estrogen administration; (3) estrogen derivatives administered to green monkeys for changes in the levels of selective plasma proteins. This work is directed toward the selection of safer yet effective estrogens that can be used with progestins as improved contraceptives.